1. Technical Field
The present invention generally relates to tropoelastin polynucleotides and polypeptides and methods of making and using the same to prepare biocompatible polymeric scaffold materials. More particularly, the present invention relates to alternative spliced tropoelastin isoforms, and to implants and grafts comprising polymeric scaffold materials of cross-linked human tropoelastin polypeptides and methods of making and using the same.
2. Description of the Related Art
Regenerative medicine has the potential to repair or replace any diseased cell, tissue, or organ; thus revolutionizing the practice of medicine. One important goal of regenerative medicine is to repair, maintain, improve or even restore the function of damaged or diseased cells, tissues, and organs. However, to date, there have a limited number of successful examples applying these concepts in a human clinical setting. In addition, many of compositions and materials used in regenerative medicine are currently cost-prohibitive, inefficient, and/or unsafe.
Surgical means have been used to regenerate tissue in a certain, controlled manner. Common reasons for surgical intervention include, a fractured bone, the regeneration of new tissue to replace tissue lost due to traumatic or surgical causes or an infection, atrophy or for congenital reasons. Success of surgical interventions often requires that the affected tissue be separated from other tissues surrounding it and that around the tissue a certain space is created, to which tissue can regenerate.
The inadequacy of existing polymeric graft materials has constantly been challenged by the development of new materials, particularly those with more favorable physical properties. The use of polyurethane biomaterials has been limited by questions surrounding long-term stability of implanted materials. The combined susceptibility of polyurethanes to hydrolysis, cracking, enzymatic degradation, calcification and corrosion to varying degrees depending on the formulation (Santerre et al., (2005), Biomaterials, 26, 7457-70) has led to doubts regarding biostability and bi-product toxicity. The problems faced by polyurethane biomaterials are common to this field.
Currently available biocompatible membranes also lack ideal shapeability and rigidity. These two properties of biocompatible membranes are contrary to each other. For example, a biocompatible membrane must naturally be shaped to fit the tissue structure in such a manner that it separates the tissues from each other exactly as desired so as to allow the regenerating tissue to grow in the correct shape with no damage to the surrounding tissue. On the other hand, the membrane must be sufficiently rigid that its shape does not change under the pressure caused by the growing tissue or that possible external stress does not cause a movement hampering the healing of the tissue. The prior art does not provide a satisfactory solution to fulfilling both requirements.
For example, synthetic biocompatible membranes made of expanded polytetrafluoroethylene (ePTFE) such as GoreTex®, Impra, or Atrium have increased rigidity when supported by titanium support threads or other metal alloys. Such membranes are often rigid and therefore keep their form well under the pressure of tissue, but correspondingly, their shaping is arduous. In contrast shaping support thread-free PTFE membranes is quite easy, but their rigidity is not sufficient. Another significant problem with such membranes is that they require surgical removal from the organ system after the tissue has healed. Surgical removal of such membranes increases patient costs, discomfort, and adds to the patient's risk of obtaining an infection from the operation.
Biocompatible membranes made of biodegradable polymers need not be surgically removed from the organ system, as they dissipate slowly from the organ system via normal biochemical and metabolic pathways. A significant problem with biodegradable materials is that the thin, easily shaping membranes are not rigid enough to maintain space for the regenerating tissue to grow undisturbed. Thus, there is a significant risk the membrane bends under pressure against the healing tissue so that there is insufficient space for the regenerating tissue to adequately grow. To achieve sufficient rigidity, the membrane can naturally be made thicker. However, when the thickness of the membrane is increased to achieve a sufficient rigidity, the membrane becomes so thick that shaping it is very difficult and arduous.
It is clear that there is a large unmet need in regenerative medicine for a more biocompatible, durable, and clinically effective polymeric biomaterial. The compositions, implants, and methods of the present invention address these needs and offer other related advantages.